Our main goal is to determine what factors allow measles virus, a virus normally producing an acute infection, to persist and produce a chronic infection such as SSPE. AS a means of answering this broad question we plan to perform comparative studies between: (1) acute, lytic infections; (2) well established persistent infections; (3) non-productive, cell-associated SSPE strains; and (4) cell/virus systems that produce immediate persistent infections. These comparative studies should provide detailed information on the biochemical events involved in the establishment and the maintenance of measles persistence. These studies will also provide us with more detailed knowledge about the mechanisms of "normal" infections. This information is crucial for an understanding of what is different in those systems that are less or that fail to efficiently release budding virus (i.e., SSPE and persistent infections in vitro). Evidence exists for the role of both the virus and the cell in measles virus persistence. Evidence for the virus's role comes from the findings that Alternations of the measles virus matrix (M) protein are associated with persistent infections of measles virus both in vitro (tissue culture) and in vivo (SSPE), and some viruses recovered from persistently infected cells have the capacity to produce persistent infections in normal cells. Evidence for the cell's role comes from the observations that wt measles virus produces immediate persistent infections in MDBK and L cells. We plan to focus on both the defects in M protein associated with persistence, and the host cell's role in persistence. We specifically wish to determine: 1) The nature of M protein variants associated with persistence. 2) The role of M protein in persistence. a) Do alterations in M protein play an important role in persistence? b) Are the normal functions of the M protein altered in persistent infections? 3) The host cell's role in measles persistence. 4) Differences between fuzzy and smooth nucleocapsids and their roles in viral maturation.